Objectives To correlate the clinicopathological background and histopathological criteria (human HIV lesion) of persistent generalized lymphadenopathy in SIV inoculated rhesus macaques which have died or been terminated under an AIDS-like syndrome, weight loss, lymphadenopathy, diarrhea, and development of lymphoma. ABSTRACT:Persistent generalized lymphadenopathy is well recognized as an early manifestation of HIV-infected patients. As the disease progresses, the early florid follicular hyperplastic lesion (type I) is transformed into an immunoblastic cell proliferative lesion with partial lymphocyte depletion (type II) and finally the nodes become burnt out, causing marked lymphocyte depletion (type III). Eighteen rhesus monkeys inoculated with SIV manifested progressive weight loss, diarrhea, lymphadenopathy, and lymphomatous lesions at 3 to 12 months after inoculation. The lymph nodes of ileocecal, mesenteric, other visceral, inguinal and axillary regions, and the spleen were observed in 17 autopsy cases and 2 biopsied nodes. After inoculation, an AIDS-like syndrome appeared at different times, after 3 to 12 months, in each individual. In histopathological study of ileocecal, mesenteric, inguinal, and axillary lymph nodes, Type I, acute lymphadenopathy, was encountered in 5 cases of monkeys which died an average 6.6 months after the inoculation. Type II, subacute lesions, were found in 5 cases (an average 9.1 months after inoculation) and type III, terminal burnt out lesions, appeared in 8 cases (an average 9 months). Two cases of lymphoma (B cell lineage) in the intraorbital cavities and lung coexisted in the animals having type II lymph node lesions manifested with diffuse lymphoblastic cell proliferation. The ileocecal lymph nodes in type II lesions usually showed the most prominent and proliferative features, though the inguinal and axillary nodes showed early signs of lymphocyte depletion in the same individual. Splenomegalia associated with lymphocyte proliferation in the follicular and periarterial lymphatic sheath was generally accompanied by type II lesions, but such hyperplastic features persisted in 4 cases showing type III lymph node lesions. Virions and viral RNA were demonstrated by an in situ hybridization technique in the follicular germinal centers and paracortical regions of the nodes of all three types. SIV caused specific clinicopathological and lymphatic regressive lesions in rhesus macaques showing immunodeficient sequela compatible with HIV infection in human patients. Keywords SIV inoculation lymphadenopathy lymphoma